INTRODUCTION — Sellar masses typically present in one or more ways:
●With neurologic symptoms, such as visual impairment, diplopia, or headache
●As an incidental finding on magnetic resonance imaging (MRI) or computed tomographic (CT) scanning performed for some other reason
●With hormonal abnormalities
This topic will review the causes, clinical manifestations, and evaluation of sellar masses. The clinical presentation and management of individual pituitary tumors, pituitary incidentalomas, and hypopituitarism are discussed separately. (See "Clinical manifestations and evaluation of hyperprolactinemia" and "Clinical manifestations and diagnosis of gonadotroph and other clinically nonfunctioning pituitary adenomas" and "Pituitary incidentalomas" and "Clinical manifestations of hypopituitarism".)
CAUSES — Pituitary adenomas are the most common cause of sellar masses from the third decade on, accounting for up to 10 percent of all intracranial neoplasms [1-3]. Other disorders, which are often difficult to distinguish from pituitary adenomas by imaging, include physiologic enlargement of the pituitary and benign and malignant tumors (table 1).
Pituitary adenomas — Pituitary adenomas are benign tumors of the anterior pituitary, but they are true neoplasms, as shown by clonality studies [4,5].
Incidence and prevalence — There are few population studies of the incidence and prevalence of pituitary adenomas. However, a population-based study in Northern Finland, where all patients within a health care district are referred to a predetermined medical center, found the following standardized incidence rates per 100,000 (cases diagnosed between 1992 and 2007) :
●All pituitary adenomas – 4.0
●Lactotroph adenomas – 2.2
●Clinically nonfunctioning adenomas – 1.0
●Somatotroph adenomas – 0.34
●Corticotroph adenomas – 0.17
Past studies of pituitary adenomas in the population are thought to have underestimated their true prevalence. In a current report from a single community of over 80,000 inhabitants in England, the prevalence of pituitary adenomas per 100,000 was fourfold higher than previous estimates :
●All adenomas – 77.6
●Lactotroph adenomas – 44.4
●Nonfunctioning adenomas – 22.2
●Somatotroph adenomas – 8.6
●Corticotroph adenomas – 1.2
Genetics — Classic oncogene mutations are rarely found in pituitary adenomas, but mutations in the following genes may play a role in the development of one or more types of pituitary adenomas:
●MEN1 – Loss-of-function mutations of this tumor suppressor gene appear to be responsible for the tumors that occur in the parathyroids, pancreatic islets, and pituitary glands of patients who have multiple endocrine neoplasia type 1 (MEN1) syndrome . However, mutations in this gene do not appear to cause sporadic pituitary adenomas . (See "Multiple endocrine neoplasia type 1: Genetics".)
●Gs-alpha – An activating mutation of the alpha subunit of the guanine nucleotide stimulatory protein (Gs-alpha) gene is found in approximately 40 percent of somatotroph adenomas [10,11]. These mutations result in constitutive activation of adenylyl cyclase, which may play a role in both cell division and excessive growth hormone secretion by these adenomas. (See "Causes and clinical manifestations of acromegaly".)
●AIP – Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) are associated with familial pituitary adenomas, usually somatotroph or somatomammotroph adenomas, that present in adolescence or early adulthood and are relatively aggressive .
Classification — Adenomas are classified by size and the cell of origin. Lesions smaller than 1 cm are classified as microadenomas, and lesions larger than 1 cm are classified as macroadenomas. Adenomas can arise from any type of cell of the anterior pituitary and may result in increased secretion of the hormone(s) produced by that cell and/or decreased secretion of other hormones due to compression of other cell types .
●Gonadotroph adenomas usually present as clinically nonfunctioning sellar masses, but rarely cause symptoms due to hormonal hypersecretion. (See "Clinical manifestations and diagnosis of gonadotroph and other clinically nonfunctioning pituitary adenomas".)
●Thyrotroph adenomas may present as clinically nonfunctioning sellar masses that secrete only alpha or TSHB subunits or may cause hyperthyroidism due to increased secretion of intact thyroid-stimulating hormone (TSH). (See "TSH-secreting pituitary adenomas".)
●Corticotroph adenomas usually cause Cushing disease, but a significant minority are "clinically silent" or totally silent. (See "Establishing the cause of Cushing syndrome" and "Clinical manifestations and diagnosis of gonadotroph and other clinically nonfunctioning pituitary adenomas".)
●Lactotroph adenomas usually cause hyperprolactinemia, which leads to hypogonadism in both females and males. (See "Clinical manifestations and evaluation of hyperprolactinemia".)
●Somatotroph adenomas typically cause acromegaly due to increased growth hormone secretion, but a significant minority are "clinically silent." (See "Causes and clinical manifestations of acromegaly" and "Clinical manifestations and diagnosis of gonadotroph and other clinically nonfunctioning pituitary adenomas".)
●Lactotroph/somatotroph adenoma combinations that secrete both prolactin and growth hormone  are well recognized and cause the clinical syndromes of both hormones. Other mixed cell adenomas, sometimes called plurihormonal adenomas, can involve any combination of cells but are uncommon.
Pituitary hyperplasia — There are several recognized causes of hyperplasia of the pituitary. These may present as sellar masses and be misdiagnosed as pituitary adenomas:
●Lactotroph hyperplasia during pregnancy. (See "Causes of hyperprolactinemia".)
●Thyrotroph and gonadotroph hyperplasia due to longstanding primary hypothyroidism and primary hypogonadism, respectively [15-19].
●Somatotroph hyperplasia due to ectopic secretion of growth hormone-releasing hormone, a rare condition .
Other benign tumors — Several other benign tumors can occur in or near the sella, including craniopharyngiomas, meningiomas, and, less commonly, pituicytomas (image 1).
Craniopharyngioma — Craniopharyngiomas are solid or mixed solid-cystic benign tumors that arise from remnants of Rathke's pouch along a line from the nasopharynx to the diencephalon. Most are either intrasellar or suprasellar (image 1).
Approximately 50 percent present clinically during childhood and adolescence, the other 50 percent present after age 20 years, some not until age 70 or 80 years. The major presenting symptoms are growth retardation in children and abnormal vision in adults. In addition, pituitary hormonal deficiencies, including arginine vasopressin deficiency (AVP-D, previously called central diabetes insipidus), are common. (See "Craniopharyngioma".)
Meningioma — A meningioma is a usually benign tumor arising from the meninges anywhere within the head. Some arise near the sella, causing visual impairment and hormonal deficiencies. (See "Epidemiology, pathology, clinical features, and diagnosis of meningioma".)
Pituicytoma — This is an uncommon, low-grade (World Health Organization [WHO] grade 1), indolent glioma arising from the pituicytes of the posterior pituitary. It presents as a sellar mass, which is usually mistaken for a pituitary adenoma, and has no known hormonal secretory function.
Malignant tumors — Some malignant tumors arise within or near the sella, and others metastasize to this site.
Primary — Malignancies that arise in the parasellar region include germ cell tumors, sarcomas, chordomas, and lymphomas. Pituitary carcinomas are rare .
●Germ cell tumors – Germ cell tumors, also called ectopic pinealomas, usually occur through the third decade of life and may present with headache, nausea, vomiting, and lethargy (from increased intracranial pressure in patients with pineal lesions); diplopia, hypopituitarism, or AVP-D (with suprasellar tumors); and paralysis of upward conjugate gaze (Parinaud syndrome). Imaging shows a mass in the third ventricle. Serum concentrations of human chorionic gonadotropin-beta (B-hCG) and/or alpha fetoprotein (AFP) may be increased. Although these lesions are highly malignant and metastasize readily, they are also highly radiosensitive. (See "Intracranial germ cell tumors".)
●Chordomas – Chordomas usually are locally aggressive tumors that can metastasize. They often arise in the clivus and present with headaches, visual impairment, and anterior pituitary hormonal deficiencies. (See "Chordoma and chondrosarcoma of the skull base".)
●Primary lymphoma – Primary central nervous system (CNS) lymphoma sometimes involves the pituitary and hypothalamus. A review of 13 patients with pituitary involvement noted neurologic symptoms (headaches and visual and oculomotor impairment) and/or deficiencies of anterior pituitary hormones and antidiuretic hormone . Magnetic resonance imaging (MRI) shows a sellar mass with variable extrasellar extension. (See "Primary central nervous system lymphoma: Clinical features, diagnosis, and extent of disease evaluation", section on 'Clinical features'.)
Metastatic disease — Metastases to the hypothalamus and pituitary gland account for 1 to 2 percent of sellar masses [1,23]. They occur most commonly with breast cancer in women and lung cancer in men but can be seen with many other cancers [24,25]. Symptoms, which occur in approximately 7 percent of patients, include AVP-D, anterior pituitary dysfunction, visual field defects, retroorbital pain, and ophthalmoplegia . Survival in 36 patients in one series averaged six months .
Cysts — Several types of cysts can occur in the sellar and/or suprasellar area, including Rathke's cleft [26,27], arachnoid , and dermoid cysts. Rathke's cleft cysts, the most common, are benign cysts derived from remnants of Rathke's pouch, the same structure from which craniopharyngiomas arise (see "Craniopharyngioma"). The clinical characteristics of all are similar.
Most cysts are small and discovered incidentally by MRI. The MRI characteristics include a sellar and/or suprasellar, symmetrical, round or ovoid mass that enhances on either T1 or T2-weighted images but does not concentrate gadolinium. Larger cysts may cause headaches, visual impairment, and/or anterior pituitary hormonal deficiencies. Rarely, they bleed, causing apoplexy, or rupture, causing aseptic meningitis.
The natural history is variable. Of 75 patients with Rathke's cleft cysts followed for a median of 24 months, 57 percent had no change in size, 28 percent increased, and 15 percent decreased .
Abscess — Pituitary abscesses, which are rare, can occur in a normal or diseased pituitary gland. In a series of 24 patients, 16 (67 percent) presented with symptoms and physical findings consistent with a pituitary mass, while only eight had features suggestive of infection (fever, leukocytosis, meningismus) . Imaging studies, including computed tomography (CT) and MRI, were unable to distinguish between pituitary abscess and pituitary adenoma. As a result, most patients were diagnosed at the time of surgical exploration.
Arteriovenous fistula of the cavernous sinus — Arteriovenous fistulae of the cavernous sinus can cause modest enlargement of the pituitary gland. Pituitary size returns toward baseline after the fistula is blocked .
Hypophysitis — Several types of hypophysitis can enlarge the pituitary early in their course. Lymphocytic infiltration of the pituitary usually occurs in late pregnancy or the postpartum period, but can also be seen in women at other times and infrequently in men  and increasingly due to anti-cytotoxic T-lymphocyte antigen (CTLA)-4 treatment of malignancies [32-34]. It is characterized by headaches of an intensity out of proportion to the size of the lesion and hypopituitarism, in which adrenal insufficiency is unusually prominent. (See "Causes of hypopituitarism", section on 'Hypophysitis' and "Toxicities associated with immune checkpoint inhibitors", section on 'Hypophysitis'.)
CLINICAL MANIFESTATIONS — Sellar masses can present with neurologic symptoms, abnormalities related to under- or oversecretion of pituitary hormones, or as an incidental finding on radiologic examination performed for some other reason.
Visual defects — Impaired vision is the most common symptom that leads a patient with a nonfunctioning adenoma, of which over 80 percent are gonadotroph adenomas, to seek medical attention . (See "Clinical manifestations and diagnosis of gonadotroph and other clinically nonfunctioning pituitary adenomas".)
Visual impairment is caused by suprasellar extension of the adenoma, leading to compression of the optic chiasm. The most common complaint is diminished vision in the temporal fields (bitemporal hemianopsia). One or both eyes may be affected and, if both, to variable degrees. Diminished visual acuity occurs when the optic chiasm is more severely compressed. Other patterns of visual loss can also occur. Thus, an intrasellar lesion should be suspected when there is any unexplained pattern of visual loss.
The onset of the visual deficit is usually so gradual that many patients do not seek ophthalmologic consultation for months or even years. Even at this time, the reason for the deficit may not be recognized, unless a visual field examination is performed, further delaying the diagnosis.
Other neurologic symptoms — Other neurologic symptoms that may cause a patient with a sellar mass to seek medical attention include:
●Headaches, presumably caused by expansion of the sella. The quality of the headache is not specific.
●Diplopia, induced by oculomotor nerve compression resulting from lateral extension of the mass.
●Pituitary apoplexy induced by sudden hemorrhage into an adenoma, causing excruciating headache and diplopia.
●Cerebrospinal fluid rhinorrhea, caused by inferior extension of the mass, an extremely uncommon presentation.
●Parinaud syndrome, a constellation of neuro-ophthalmologic findings (most often paralysis of upward conjugate gaze), that result from ectopic pinealomas. (See "Ocular gaze disorders", section on 'Parinaud syndrome'.)
Hormone deficiencies — At the time of initial presentation with a neurologic symptom, many patients with sellar masses, when carefully questioned, admit to symptoms of pituitary hormone deficiencies. However, these symptoms are not usually the reason that the patient seeks medical attention.
The most common pituitary hormone deficiencies are of gonadotropins, resulting in hypogonadism in both males and females.
EVALUATION OF A SELLAR MASS — Sellar masses should be evaluated both radiologically and hormonally.
MRI — Magnetic resonance imaging (MRI) with gadolinium is the single best imaging procedure for most sellar masses, and there is usually no need to perform any other imaging study. Certain MRI findings suggest a greater likelihood of some kinds of sellar masses than others . As an example, a mass that is separate from the pituitary gland generally indicates that the mass is not a pituitary adenoma (image 2). However, no finding is usually pathognomonic of any one kind of mass (image 2 and image 3 and image 4). In situations in which the use of gadolinium is contraindicated, such as renal impairment or pregnancy, MRI without gadolinium may still be helpful.
Unenhanced image — Normal pituitary tissue and most sellar lesions, pituitary adenomas, and other tumors, have a signal that is similar to or slightly greater in intensity than that of central nervous system (CNS) tissue. Cystic lesions, such as Rathke's cleft cysts, often have a low-intensity signal on T1-weighted images; however, craniopharyngiomas and even pituitary adenomas may be partially cystic and, therefore, have low-intensity signals. Furthermore, the signal intensity on T1-weighted images will be high if the protein or lipid concentration of the cyst fluid is high. On T2-weighted images, cystic lesions may have a high-intensity signal. Hemorrhage into the pituitary gland results in a high-intensity signal on both T1- and T2-weighted images.
Meningiomas typically have a brighter and more homogeneous signal than pituitary adenomas. They also have a suprasellar rather than a sellar epicenter and a dural-based attachment best seen after contrast enhancement .
Gadolinium-enhanced image — Normal pituitary tissue takes up gadolinium to a greater degree than CNS tissue and therefore has a higher-intensity signal than the surrounding CNS. Both micro- and macroadenomas of the pituitary (as well as other sellar masses such as craniopharyngiomas and meningiomas) usually take up gadolinium to a lesser degree than the normal pituitary but more than the CNS. Therefore, the degree of gadolinium enhancement does not distinguish one kind of sellar mass from another. The postcontrast enhancement of meningiomas is usually homogeneous. If a sellar lesion can be seen as separate from the normal pituitary, whether on unenhanced or, more commonly, enhanced images, the lesion is usually not a pituitary adenoma.
Among patients with moderate to advanced renal failure (dialysis-dependent or estimated glomerular filtration rate [eGFR] less than 30 mL/min), the administration of gadolinium has been associated with the potentially severe syndrome of nephrogenic systemic fibrosis. In such patients, gadolinium-based imaging should be avoided if possible. This issue, as well as the role of hemodialysis after the procedure if gadolinium-based imaging must be performed, is discussed separately. (See "Patient evaluation before gadolinium contrast administration for magnetic resonance imaging", section on 'Approach to preventing nephrogenic systemic fibrosis' and "Nephrogenic systemic fibrosis/nephrogenic fibrosing dermopathy in advanced kidney disease", section on 'Prevention'.)
Hormonal evaluation — We recommend evaluation of hypothalamic-pituitary hormonal function whenever a sellar mass is encountered. Hormonal hypersecretion is caused only by pituitary adenomas. Consequently, the demonstration of hormonal hypersecretion identifies the sellar mass as a pituitary adenoma and also identifies the type of adenoma.
We therefore suggest measurements of serum prolactin (lactotroph adenomas), insulin-like growth factor-1 (IGF-1) (somatotroph adenomas), and plasma corticotropin (ACTH) and 24-hour urinary free cortisol (corticotroph adenomas).
Additional endocrine testing is needed when a gonadotroph or thyrotroph adenoma is suspected (luteinizing hormone [LH], follicle-stimulating hormone [FSH], total or free thyroxine [T4], and thyroid-stimulating hormone [TSH], respectively). Testing of alpha subunit is needed when either type of adenoma is suspected. (See "Clinical manifestations and diagnosis of gonadotroph and other clinically nonfunctioning pituitary adenomas" and "TSH-secreting pituitary adenomas".)
Hormonal hypersecretion — Hypersecretion, with the exception noted below, is caused only by pituitary adenomas. As a result, the demonstration of hormonal hypersecretion identifies both the sellar mass as a pituitary adenoma and the kind of adenoma:
●A serum prolactin concentration >200 ng/mL generally identifies a lactotroph adenoma; values that are between 20 and 200 ng/mL could be due to a lactotroph adenoma or to any other sellar mass or medications. (See "Clinical manifestations and evaluation of hyperprolactinemia", section on 'Serum prolactin concentrations'.)
●The best single test for the diagnosis of acromegaly is measurement of serum IGF-1. Among patients with equivocal values, serum growth hormone levels can be measured after an oral glucose load. (See "Diagnosis of acromegaly".)
●Elevated 24-hour urine cortisol excretion associated with a high-normal or high ACTH concentration usually indicates a corticotroph adenoma. (See "Establishing the diagnosis of Cushing syndrome" and "Establishing the cause of Cushing syndrome".)
●Gonadotroph adenomas can be identified by characteristic patterns of basal and thyrotropin-releasing hormone (TRH)-stimulated concentrations of gonadotropins and their subunits; these patterns differ somewhat in males and females. TRH is not currently available in the United States but is still available in many other countries. (See "Clinical manifestations and diagnosis of gonadotroph and other clinically nonfunctioning pituitary adenomas".)
●Thyrotroph adenomas are characterized by a clinically hyperthyroid patient who has a diffuse goiter and elevations in serum free T4 and triiodothyronine (T3) but an inappropriately normal or elevated serum TSH level. (See "TSH-secreting pituitary adenomas".)
Hormonal hyposecretion — In addition to testing for hormonal hypersecretion, the possibility of hormonal hyposecretion should be evaluated in all patients who have a sellar mass >1 cm in order to identify and replace hormonal deficiencies (see "Diagnostic testing for hypopituitarism"). The presence of hormonal deficiencies, however, is not generally useful in the differential diagnosis of a sellar mass, since any mass can cause these deficiencies. One exception to this statement is that the spontaneous development of arginine vasopressin deficiency (AVP-D) indicates that the lesion affects the hypothalamus or the stalk and is therefore not a pituitary lesion. (See "Arginine vasopressin deficiency (central diabetes insipidus): Clinical manifestations and causes".)
Pituitary incidentaloma — The extent of the evaluation in a patient with an incidentally discovered intrasellar MRI signal abnormality depends upon its size. If it is larger than 1 cm, it should be evaluated as described above. If the mass is smaller than 1 cm, especially much smaller, and the patient has no clinical findings of pituitary dysfunction, we usually measure only the serum prolactin concentration, which, in one report, was much more cost effective than either measurement of multiple hormones or performance of follow-up MRIs at 6 and 12 months . One exception may be the patient who is quite anxious about the presence of a small pituitary tumor. No evaluation for hormonal hyposecretion or visual abnormalities is necessary. (See "Pituitary incidentalomas".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pituitary tumors and hypopituitarism".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Prolactinoma (The Basics)" and "Patient education: Pituitary adenoma (The Basics)")
●Beyond the Basics topics (see "Patient education: High prolactin levels and prolactinomas (Beyond the Basics)" and "Patient education: Acromegaly (Beyond the Basics)" and "Patient education: Meningioma (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Pituitary adenomas – Sellar masses usually present with neurologic symptoms, hormonal abnormalities, or as an incidental finding on magnetic resonance imaging (MRI). Pituitary adenomas are the most common cause of sellar masses, but other causes include:
•Physiologic enlargement of the pituitary – Physiologic enlargement of the pituitary, most commonly during pregnancy, but also in primary hypothyroidism and primary hypogonadism. (See "Causes of hyperprolactinemia".)
•Benign tumors – Other benign tumors, such as craniopharyngioma and meningioma (image 1). (See "Craniopharyngioma" and "Epidemiology, pathology, clinical features, and diagnosis of meningioma".)
•Malignant tumors – Malignant tumors, both primary (germ cell tumor, chordoma, primary central nervous system [CNS] lymphoma) and metastatic (most commonly from breast and lung cancer). (See "Intracranial germ cell tumors" and "Primary central nervous system lymphoma: Clinical features, diagnosis, and extent of disease evaluation" and "Chordoma and chondrosarcoma of the skull base".)
•Hypophysitis – Hypophysitis, especially lymphocytic (lymphocytic infiltration of the pituitary), occurs most commonly in postpartum women but can also be seen in women at other times, and rarely in men but increasingly due to anti-cytotoxic T-lymphocyte antigen (CTLA)-4 treatment of malignancies. (See 'Hypophysitis' above and "Causes of hypopituitarism".)
•Other – Sellar masses may also be due to a cyst, abscess, or arteriovenous fistula of the cavernous sinus. (See 'Cysts' above and 'Abscess' above and 'Arteriovenous fistula of the cavernous sinus' above.)
•MRI – We recommend MRI with gadolinium as the single best and usually only imaging procedure for most sellar masses. Certain MRI findings suggest a greater likelihood of some kinds of sellar masses than others. As an example, finding a mass that is separate from the pituitary gland generally indicates that the mass is not a pituitary adenoma.
•Test for hormonal hypersecretion – We recommend evaluation of hypothalamic-pituitary hormonal function whenever a sellar mass is encountered. Hormonal hypersecretion is caused only by pituitary adenomas. Consequently, the demonstration of hormonal hypersecretion identifies the sellar mass as a pituitary adenoma and also identifies the type of adenoma. (See 'Hormonal evaluation' above.)
Hormonal hyposecretion may be caused by any hypothalamic or pituitary lesion and therefore usually has no value in the differential diagnosis of a sellar mass. One exception to this statement is that the spontaneous development of arginine vasopressin deficiency (AVP-D) indicates that the lesion affects the hypothalamus or the stalk and is therefore not a pituitary lesion. (See "Arginine vasopressin deficiency (central diabetes insipidus): Clinical manifestations and causes".)
•Importance of size – The extent of the evaluation in a patient with an incidentally discovered intrasellar MRI signal abnormality (pituitary incidentaloma) depends upon its size. If it is larger than 1 cm, we recommend evaluating for hormonal hypersecretion and hyposecretion as described above (see 'Hormonal evaluation' above). If it is smaller than 10 mm and the patient has no clinical findings of pituitary dysfunction, we recommend measuring only the serum prolactin concentration. (See "Pituitary incidentalomas".)
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